Analysis of Clinical Features, Laboratory Characteristics and Therapeutic Outcome in Patients with Thrombotic Thrombocytopenic Purpura Treated at King Fahad Medical City, Riyadh, Saudi Arabia

Abstract Background Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by microvascular platelet deposition and thrombus formation with resulting microangiopathic hemolytic anemia and thrombocytopenia. Deficiency of the von Willebrand factor cleavage metalloprotease, also known as ADAMTS 13, has been implicated as an important etiological factor in TTP. Few small studies have been reported on Saudi patients with TTP until now. Our aim was to analyze the clinical features, laboratory characteristics and treatment outcomes with TTP patients treated at our large tertiary care center. Methods This is retrospective data of 24 patients with diagnosed of TTP who were treated at King Fahad Medical City, Riyadh, Saudi Arabia between October 2006 and April 2015. Patient suspected as a case of TTP on the basis of clinical features with the evidence of microangiopathic hemolysis and thrombocytopenia were included in this study although data related to pentad of TTP was collected and wherever logistically possible ADAMTS13 levels and inhibitor titer were determined. The primary aim was outcome assessment by overall response rate (ORR) in the treated patients through Kaplan-Meier method. Paired sample t-test was applied to determine the mean significant difference among platelets (plt), hemoglobin (Hgb) & LDH on day 1 and day 7 of treatment. Results Twenty-four TTP patients (18 females; 6 males) admitted to our hospital from 2006 to 2015 were analyzed. The mean age was 33.5±13.9 years. Twenty-two (91%) of the patients presented with neurologic features, seven (29%) had fever, ten (42%) had renal impairment that normalized with treatment and four (20.83%) had increased troponin-T or cardiac symptoms. There were 22 patients (91.7%) with the triad of TTP, including hemolytic anemia, thrombocytopenia and neurologic abnormalities; only 2 (8.2%) had the classical pentad of TTP. Among the plausible etiology, idiopathic (51.8%) was the most common followed by acquired autoimmune abnormalities (29.2%). Plasma ADAMTS 13 activity was determined in 19 patients. Eight patients (42.1%) had severe ADAMTS 13 deficiency (activity< 5%); 5 (26.3%) had moderate decrease of ADAMTS 13 activity (activity: 5-10%); another 3 (15.8%) had low ADAMTS 13 activity and 3 (15.8%) patients had normal ADAMTS 13 (>50%) most likely due to sampling post plasma infusion in emergency situations. Median platelet count on Day 1 was 14x10^9/L, and Day 7 was 119x10^9/L (P value< 0.001), Median Hgb on Day1 was 8.25 gm/dl and Day 7 was 9.35 gm/dl (P value< 0.007), Median LDH on Day 1 was 1211 IU/L and Day7 was 278.92 IU/L (P value< 0.001) respectively. All patients received plasma exchange whereas 23 (95.8%) patients received adjunctive corticosteroids. Five patients (20.8%) were early refractory to standard treatment with therapeutic plasma exchange (TPE). Thirteen (54.2%) patients received rituximab either due to refractoriness to TPE on ~ day 7, or earlier due to cardiac or neurological manifestations at treating physician's discretion. Average hospital stay was 27 days (range 1-131). Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. On long term follow up of 22 months (median, Range 1-113), overall survival was 80%. Three patients died during acute episode because of very sever disease or delayed arrival to our center. One patient died later on because of other comorbidities while in CR. Conclusion Thrombotic thrombocytopenic purpura is a life threatening condition and immediate treatment with plasma exchange along with steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of our patients. Combination of very severe CNS manifestations and delayed arrival contributed to mortality significantly. More awareness is needed for early diagnosis and early referral to higher centers. Disclosures No relevant conflicts of interest to declare.

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Association of Plasmic Score with Neurological Symptoms in Patients with Thrombotic Thrombocytopenic Purpura (TTP)

Blood ◽

10.1182/blood-2019-129144 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4894-4894

Author(s):

Jose Thiago de Souza Castro ◽

Letícia Rittner ◽

Simone Appenzeller ◽

Gabriela G Yamaguti-Hayakawa ◽

Marina Colella ◽

...

Keyword(s):

Regression Analysis ◽

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Clinical Features ◽

Odds Ratio ◽

Neurological Complications ◽

Neurological Symptoms ◽

Thrombocytopenic Purpura ◽

The Mean ◽

Immunosuppression Therapy

The PLASMIC score was recently developed for rapid diagnosis of thrombotic thrombocytopenic purpura (TTP) and therapeutic decision, as ADAMTS13 is frequently unavailable. The score consists of a scale from 1 to 7 that considers clinical and laboratory factors. PLASMIC score 6 - 7, 4 - 5 and below 4 are associated with high, intermediate and low probability of ADAMTS13 deficiency, respectively. Although the PLASMIC score is validated to predict ADAMTS13 values, its role as a predictor of adverse clinical outcomes in TTP is not established. The primary aim of this study was to evaluate whether the PLASMIC score is associated with neurological complications during TTP episodes. We also evaluated the association of the score with treatment outcomes, such as number of plasma exchange procedures, need for a second line immunosuppression therapy, days in hospital and death. In the present study, we retrospectively applied the PLASMIC score at the time of diagnosis of TTP episodes treated at the UNICAMP Clinical Hospital (University of Campinas - Brazil) between 1995 and 2016. All clinical data were retrieved from medical charts. We grouped the episodes according to the PLASMIC score, calculated at diagnosis, and compared the occurrence of neurological symptoms and other clinical manifestation between the PLASMIC score groups. The association between the PLASMIC score and neurological symptoms was evaluated by regression analysis. A total of 50 episodes of TTP were identified, of these 47 episodes, and 34 patients, were included in the study. Three episodes were excluded due to lack of clinical data. Twenty-seven (79.4%) patients were women, and the mean age was 35.7 years (SD 12.7). At the diagnosis, the mean PLASMIC score was 6, no PLASMIC score below 4 was detected, and the most common clinical features were thrombocytopenia (mean platelet count = 21,029 x 109 / L [SD 18,371 x 109]) and reticulocytosis (mean count = 7.83% [SD 5.29]). Plasma exchange was the main treatment in 98% of the episodes and an immunosuppression therapy was used in 94% of the cases. In 74.5% of the episodes, the patients presented with neurological symptoms at diagnosis or during hospitalization. Clinical features at diagnosis and during hospitalization of all TTP episodes, and of TTP episodes grouped according to the initial PLASMIC score, are presented in Table 1. The incidence of neurological symptoms was higher in PLASMIC score 7 (n= 14 [87, 5%]) and 6 (18 [81, 8%]) when compared with scores 5 (n=1, [16.7%) and 4 (n= 2 (66.7%]). The neurological complications tended to be more severe in PLASMIC scores 6 and 7. Personality change was reported in 2 (9%) TTP episodes in which the PLASMIC score was 6, in 4 (25%) episodes in which the PLASMIC score was 7 and was not reported in PLASMIC scores 4 and 5. Sensitivity loss was reported in 1 (16%) TTP episode in which the PLASMIC score was 5, in 11 (50%) episodes in which the PLASMIC score 6, and in 10 (62%) episodes in which the PLASMIC score was 7 . Seizures were reported in 3 (13.6%) TTP episodes in which the PLASMIC score was 6, in 5 (31.2%) episodes in PLASMIC score 7 and was not reported in PLASMIC scores 4 and 5. Stupor or coma were reported only in PLASMIC scores 6 [n=7 (31%]) and 7 (n= 9 [56%]). The mean number of plasma exchange procedures was 10.67 (SD=4.93) in PLASMIC score 4, 5 (SD=4.94) in PLASMIC score 5, 18.38 (10.61) in PLASMIC score 6 and 7.94 (SD=5.27) in PLASMIC score 7. The length of hospitalization and the days in intensive care unit were similar between groups. Deaths during hospitalization occurred only in cases with PLASMIC score 6 or 7. In the regression analysis, the risk of neurological complications was 9.0-fold increased (95%CI 1.6 - 52.3) in PLASMIC score 6 and was 14-fold increased (95%CI 1.8 - 106.5) in PLASMIC score 7, when compared with PLASMIC score 4 and 5. The risk of severe neurological complications was also higher in PLASMIC score 6 (odds ratio 12.0, 95% CI 1.7 - 83.5) and 7 (odds ratio 18.0, 95% CI 2.0 - 161.0) as compared to PLASMIC score 4 and 5. In conclusion, the frequency and severity of neurological injuries increased with higher PLASMIC scores. These observations suggest that further attention to neurological complications are needed when PLASMIC score is 6 or 7. Awareness of the risk of neurological complications may also improve treatment. Therefore, the PLASMIC score may be an important tool not only to predict ADAMTS13 values but also to provide information on prognosis from a neurological point of view. Disclosures No relevant conflicts of interest to declare.

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Pembrolizumab-induced thrombotic thrombocytopenic purpura

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219887212 ◽

2019 ◽

Vol 26 (5) ◽

pp. 1237-1240 ◽

Cited By ~ 4

Author(s):

Marcus SR Dickey ◽

Anant J Raina ◽

Peter J Gilbar ◽

Brendan L Wisniowski ◽

Joel T Collins ◽

...

Keyword(s):

Adverse Events ◽

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Oral Prednisolone ◽

Autoimmune Disorder ◽

Community Acquired Pneumonia ◽

Thrombocytopenic Purpura ◽

Life Threatening

Introduction Pembrolizumab is a humanised monoclonal antibody targeting the receptor programmed cell death protein-1 (PD-1), with anti-tumour activity demonstrated for many malignancies. Such immune checkpoint inhibitors are associated with many immune-related adverse events including rash, colitis, hepatitis, pneumonitis, endocrinopathy and, rarely, haematological adverse events, including immune-related thrombocytopenia. Case report We report a 60-year-old female with metastatic non-small cell lung cancer treated with pembrolizumab every three weeks. Following her fifth cycle, she presented to our hospital with community-acquired pneumonia. Thrombocytopenia developed the next day and, after detailed investigations, thrombotic thrombocytopenic purpura was diagnosed. Management and outcome Pembrolizumab was immediately ceased and plasma exchange commenced along with IV methylprednisolone 250 mg daily for three days followed by oral prednisolone. After five days of plasma exchange, platelet counts normalised and haemolytic anaemia resolved. Discussion Acquired thrombotic thrombocytopenic purpura is an autoimmune disorder caused by an inhibitory autoantibody against ADAMTS-13. While most cases of acquired thrombotic thrombocytopenic purpura are idiopathic, certain conditions (e.g. bacterial infection, autoimmune disorders, malignancies) and medications are associated with thrombotic thrombocytopenic purpura. Other potential causes were eliminated in our patient. As acquired thrombotic thrombocytopenic purpura is an autoimmune disorder, pembrolizumab, given its unique mechanism of action and association with immune-related adverse events, is believed to be implicated in the development of thrombotic thrombocytopenic purpura. This case is one of only two linking anti-PD-1 therapy to thrombotic thrombocytopenic purpura development (the other occurring in a patient on nivolumab plus ipilimumab). Thrombotic thrombocytopenic purpura is life-threatening and clinicians are advised to be aware of its possible occurrence in immune checkpoint inhibitor-treated patients.

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Critical Care COVID-19 Patient with a Picture of Thrombotic Thrombocytopenic Purpura

European Journal of Case Reports in Internal Medicine ◽

10.12890/2020_002143 ◽

2020 ◽

Author(s):

Rehab AL-Ansari ◽

Mohanad Bakkar ◽

Leena Abdalla ◽

Khaled Sewify

Keyword(s):

Mechanical Ventilation ◽

Critical Care ◽

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Kidney Injury ◽

Therapeutic Plasma Exchange ◽

Thrombocytopenic Purpura ◽

Threatening Condition ◽

Life Threatening

Background: Thrombotic thrombocytopenic purpura (TTP) is an uncommon haematological disease which can occur at any age and may present with COVID-19. This case describes a COVID-19 complication associated with a presentation resembling TTP. Case description: A 51-year-old man who had received a kidney transplant and was on immunosuppressant medication, was admitted to a critical care unit with severe COVID-19 pneumonia/acute respiratory distress syndrome (ARDS) which required intubation, mechanical ventilation and inotropic support. The course was complicated by the classic pentad of thrombocytopenia, intravascular haemolysis, acute kidney injury, neurological symptoms and fever, which prompted the diagnosis of probable TTP. After five sessions of therapeutic plasma exchange, the patient’s general status improved, he was weaned off mechanical ventilation and his renal panel and haemolytic markers normalized. Conclusion: TTP is a life-threatening condition which requires urgent management with therapeutic plasma exchange. This case highlights some possible complications of COVID-19 generally and in immunocompromised patients specifically. The potential role of plasma exchange in COVID-19 patients without a positive diagnosis of TTP (the so-called ‘TTP resembling presentation’) is an area of further research.

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Occult Disseminated Metastatic Breast Carcinoma Presenting as Acquired Thrombotic Thrombocytopenic Purpura

Case Reports in Oncology ◽

10.1159/000521159 ◽

2021 ◽

pp. 1814-1820

Author(s):

Siew Lian Chong ◽

Asral Wirda Ahmad Asnawi ◽

Roszymah Hamzah ◽

Pek Kuen Liew ◽

Tee Chuan Ong ◽

...

Keyword(s):

Breast Carcinoma ◽

Thrombotic Thrombocytopenic Purpura ◽

Hemolytic Anemia ◽

Metastatic Breast ◽

Metastatic Carcinoma ◽

Blood Film ◽

Thrombocytopenic Purpura ◽

Metastatic Breast Carcinoma ◽

Threatening Condition ◽

Life Threatening

Cancer-related microangiopathic hemolytic anemia (MAHA) is a rare and life-threatening condition. We present a patient who had been treated for invasive lobular breast carcinoma in clinical remission with fever and hemolytic anemia. The peripheral blood film showed MAHA and thrombocytopenia, and a functional deficiency of ADAMTS13 activity of 23% consistent with acquired thrombotic thrombocytopenic purpura. Bone marrow aspirate and trephine biopsy confirmed metastatic carcinoma. Further evaluation revealed the involvement of multiple bone sites without recurrence of the primary tumor. The patient received a daily plasma exchange with cryosupernatant and was pulsed with corticosteroids. MAHA related to breast cancer appears to be a rare occurrence.

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Thrombotic Thrombocytopenia Purpura Case Series in Skmc 2016-2017

Blood ◽

10.1182/blood-2019-126479 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4799-4799

Author(s):

Mohamed Abu Haleeqa ◽

Hanan Al Raeesi ◽

Fatima Alkaabi

Keyword(s):

Renal Failure ◽

Mortality Rate ◽

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Hemolytic Anemia ◽

Case Series ◽

Therapeutic Plasma Exchange ◽

Microangiopathic Hemolytic Anemia ◽

Thrombocytopenic Purpura ◽

Patient Reported

Background and Purpose Thrombotic thrombocytopenic purpura (TTP) is a heterogeneous disease primarily characterized by thrombocytopenia and microangiopathic hemolytic anemia. Therapeutic plasma exchange has dramatically improved mortality, allowing for emergence of refractory, relapsing, and atypical presentations. in this case series we aim to present our institutional data for Apheresis in Sheikh khalifa medical City in AbuDhabi. We will also present patient demographic and clinical presentation and treatment protocol we use Methodology -Case series with Retrospective review. -Routine laboratory tests such as peripheral blood cell counts, reticulocyte count, coagulation profile, serum lactate dehydrogenase (LDH), bilirubin, serum creatinine, cardiac enzymes, and urinalysis, were performed. -ADAMTS13 levels and inhibitor titer were determined for all patient in outside lab -Baseline demographic characteristics were calculated in frequencies and percentages. (include age ,Gender , clinical manifestations and treatment strategy) Results and Discussions thrombotic thrombocytopenic purpura (TTP) pentad consisting of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological abnormalities, and renal failure. less than 5 % of patient reported in literature have all associated clinical features. -Total of 10 patients M:F 4:2 , Median Age 44yr 50% presented with Neurological manifestations and renal disease , 30% presented with Fever only 20% had cardiac manifestation on admission . None of the patient presented with all 5 pentad. -All patients received TPE , steroid . -90 % of the patients received Rituximab except for 1 because of Allergy. -All patients has low ADAMTS 13 , except one has normal ADAMTS13 but came with relapse and on first admission had low ADAMTS13 -All patient presented with MAHA and TCP except 2 patient whom had normal Hb but significant schistocytes on peripheral blood with TCP both patient where relapsed cases. -3 patient were relapsed 7 de novo , the 3 relapsed cases all did not receive Rituximab in first remission . One of them relapsed twice but did not received Rituximab due to allergy -Although some publication include large number of TTP patients, but only few case reports have evaluated the clinical feature, laboratory parameters and therapeutic outcome of TTP. Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange (TPE) mortality decreases to about 10%-20%. A disintegrin and metalloprotease with thrombospondin Type 1 motif, Member 13 (ADAMTS13) levels less than 5% are a hallmark of TTP. We do ADAMTS 13 Activity and inhibitor titre levels in outside facility TAWAM hospital with turn-around time of 7 days which is helpful in planning Rituximab treatment. with availability of Rituximab our relapse rates are low but not zero Conclusions -Thrombotic thrombocytopenic purpura (TTP) pentad consisting of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological abnormalities, and renal failure. -5 % of patient reported in literature have all associated clinical features. -We found that majority of patient presented with evidence of thrombocytopenia and MAHA only. -Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange (TPE) mortality decreases to about 10%-20%. -TPE ,steroid and rituximab was very effective in achieving sustain remission in 100% of ours patients with median follow up 8 month -More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities. Figure Disclosures No relevant conflicts of interest to declare.

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Rapid Turnaround ADAMTS13 Testing Is Likely to Improve Diagnosis of Thrombotic Thrombocytopenic Purpura and Avoid Unnecessary Plasma Exchange

Blood ◽

10.1182/blood-2020-140135 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 5-6

Author(s):

Eric McGinnis ◽

Spencer D. Martin ◽

Tyler W. Smith

Keyword(s):

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Blood Product ◽

Vancouver General Hospital ◽

Adamts13 Activity ◽

Clinical Tool ◽

Thrombocytopenic Purpura ◽

Hospital Patients ◽

Life Threatening ◽

Exposure Risks

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA) resulting from severe ADAMTS13 deficiency, which is generally treated with therapeutic plasma exchange (PLEX). Although ADAMTS13 activity is often assayed to differentiate TTP from TMAs not requiring PLEX, technical and logistical constraints often limit rapid turnaround of results, with PLEX initiated based on clinical suspicion of TTP while awaiting ADAMTS13 activity results. We estimated the potential reduction in plasma product use if rapid turnaround ADAMTS13 activity testing were available in our centre. Methods: We reviewed medical records for all Vancouver General Hospital patients with ADAMTS13 activity testing since assay implementation. Patients receiving PLEX but ultimately diagnosed with a disease not requiring PLEX were identified as "potentially avoidable PLEX" (paPLEX), and their plasma product exposures and related blood product costs were estimated. Laboratory results, ADAMTS13 activity, and PLASMIC scores (a validated clinical tool for TTP diagnosis) of this group were compared to those of newly diagnosed TTP patients (N=35). Results: We identified 16 paPLEX patients, including TMAs secondary to malignant hypertension, infection, hemolytic uremic syndrome, illicit drug use, autoimmune renal disease, and malignancy (Table 1). These patients underwent 104 total PLEX cycles (3-12 per patient, median 6), involving 1,428 plasma units (28-199 per patient, median 71.5) and estimated product-associated costs of $187,759 CAD ($140,889 USD). Median platelet counts were significantly lower in TTP than the paPLEX group (7x109/L versus 38x109/L), as was serum creatinine (98µmol/L versus 224µmol/L). PLASMIC scores indicating low or intermediate likelihood of TTP were observed in 63% of patients receiving paPLEX and 17% of patients with TTP. All patients with TTP had ADAMTS13 activity < 10%, while all patients receiving paPLEX had ADAMTS13 activity ≥ 30%. Conclusions: Unnecessary PLEX carries significant patient blood product exposure risks and system costs that may be circumvented if TTP can be reliably distinguished from other TMAs at the time of initial presentation. In our cohort, ADAMTS13 activity results provided clear separation of these groups and improved upon TTP diagnosis by clinical judgement and PLASMIC scores. Rapid turnaround of ADAMTS13 activity testing results has the potential to reduce the unnecessary costs and blood product exposures resulting from PLEX administration to patients with non-TTP TMAs. Figure 1 Disclosures Smith: Alexion: Other: Participated in an advisory board without receiving financial compensation.

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Thrombotic thrombocytopenic purpura with typical pentalogy in a child: a case report and literature review

10.21203/rs.3.rs-1000584/v1 ◽

2021 ◽

Author(s):

Qian Wan ◽

Yao Ye ◽

Xiaohong Zhong ◽

Zhongjin Xu ◽

Jian Li

Keyword(s):

Case Report ◽

Literature Review ◽

Renal Insufficiency ◽

Thrombotic Thrombocytopenic Purpura ◽

Hemolytic Anemia ◽

Thrombotic Microangiopathy ◽

Typical Case ◽

Microangiopathic Hemolytic Anemia ◽

Thrombocytopenic Purpura ◽

Life Threatening

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy with clinical quintuple symptoms, including fever, thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, and renal insufficiency. TTP onset in children is rare, and the percentage of acute TTP with these five symptoms at the same time is <10%. In this study, we reported a typical case of TTP onset in a child with clinical quintuple symptoms.

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Thrombotic Thrombocytopenic Purpura in a Patient with Sickle Cell Crisis.

Blood ◽

10.1182/blood.v108.11.3963.3963 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3963-3963

Author(s):

Jumana S. Chatiwala ◽

Gunwant Guron ◽

Ibrahim Sidhom

Keyword(s):

Platelet Count ◽

Sickle Cell Disease ◽

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Hemolytic Anemia ◽

Sickle Cell ◽

Microangiopathic Hemolytic Anemia ◽

Cell Disease ◽

Thrombocytopenic Purpura ◽

Sickle Cell Crisis

Abstract Thrombotic thrombocytopenic purpura (TTP) in association with sickle cell crisis is rare. We present a case of sickle cell crisis and TTP. This is 48 years old Nigerian male with history of mild sickle cell anemia since childhood presented with sickle cell crisis and mental state changes. On admission labs are hematocrit of 20 and platelet count of 212,000. He was treated for sickle cell crisis but developed acute dysuria and progressively worsening anemia (Hct-13.7) and thrombocytopenia (Plt-9000) with sickle cell and fragmented RBCs on peripheral smear with LDH of 8772. This picture was consistent with TTP. Patient was immediately started on plasma exchange. Patient received a course of plasma exchange as well as hemodialysis and his condition improved, with return of platelet count to normal (232), LDH to baseline (276). Patient was discharged with mild renal insufficiency (serum creatinine-2.3) off dialysis and plasma exchange. Conclusion: TTP is a micro vascular occlusive disorder characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. It is associated with pentard of signs and symptoms: thrombocytopenia, microangiopathic hemolytic anemia (schistocytes on peripheral blood smear), neurological abnormalities, renal failure and fever. In practice thrombocytopenia, microangiopathic hemolytic anemia and elevated lactate dehydrogenase levels are often sufficient for the diagnosis. Our patient with sickle cell crisis was a diagnostic challenge and it is our belief that TTP evolved during inpatient therapy for painful crisis. We believe his hemolysis was due to sickle cell disease and TTP. The syndrome was reversed with prompt and aggressive treatment with plasmapharesis. (1, H. E. Lee, V. J. Marder, L. J. Logan, S. Friedman, B. J. Miller, Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease. Ann Hematol. 2003 Nov 82(11): 702–4. 2, Epub 2003 Aug 16. Chehal A, Taher A, Shamseddine A, Sicklemia with multi-organ failure syndrome and thrombotic thrombocytopenic purpura. Hemoglobin. 2002 Nov; 26(4): 345–51. 3, J. Bolanos-Meade, Y. K. Keung, C. Lopez-Arvizu, R. Florendo, E. Cobos, Thrombotic thrombocytopenic purpura in a patient with sickle cell crisis. Ann Hematol. 1999 Dec 78(12): 558–9. 4, Geigel EJ, Francis CW, Reversal of multiorgan system dysfunction in sickle cell disease with plasma exchange. Acta Anaesthesiol Scand. 1997 May; 41(5): 647–50.)

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Relationship between Hospital Volume and Inpatient Mortality Among Patients Diagnosed with Thrombotic Thrombocytopenic Purpura (TTP) in the United States

Blood ◽

10.1182/blood.v130.suppl_1.675.675 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 675-675

Author(s):

Smith Giri ◽

Ranjan Pathak ◽

Robert Franklin ◽

Nikolai A. Podoltsev ◽

Scott Huntington ◽

...

Keyword(s):

Mortality Rate ◽

Thrombotic Thrombocytopenic Purpura ◽

Hospital Volume ◽

The United States ◽

Secondary Outcome ◽

P Value ◽

Inpatient Mortality ◽

Thrombocytopenic Purpura ◽

Significant Difference ◽

The Mean

Abstract Introduction: Thrombotic Thrombocytopenic Purpura (TTP) is a hematological emergency with high inpatient mortality that requires prompt diagnosis and treatment. Studies outside the setting of hematologic emergencies have established hospital volume as a factor associated with clinical outcomes. We tested whether hospital volume was associated with important inpatient outcomes among patients with TTP Methods: We utilized the Nationwide Inpatient Sample (NIS) to identify adult patients ≥18 years, diagnosed with TTP using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 446.6 from the years of 2010 to 2013. We only included patients who received therapeutic plasmapheresis (ICD-9-CM procedure code 99.71) during hospitalization to capture active cases of TTP and improve coding accuracy. Using unique hospital identifier, hospital volume was computed and defined as total hospitalizations for TTP per year. Hospital volume was then divided into four quartiles. The primary outcome of interest was inpatient mortality rate, with time to initiation of plasmapheresis as our secondary outcome. Baseline age, gender, race, demographics, insurance payer, hospital region, hospital type (rural versus urban, teaching versus non-teaching), and bed size were collected. All analyses were survey adjusted to account for the complex sampling nature of the database. Appropriate bivariate methods included ANOVA and tests of trend (nptrend). Mixed effects hierarchical logistic regression analysis was used to calculate adjusted odds ratio of in-hospital mortality adjusting for potential confounders at the patient level (age, race, comorbidity, gender, insurance status) and at the hospital level (hospital location, bedsize and teaching status). All p values were two sided and the level of significance was chose was 0.05. Results: A total of 1128 unique hospitalizations for TTP were identified during the study period. The mean age was 46.3 ± 16.6 years, out of which 66% were females (n=754) and 44% were whites (n=458). The overall inpatient mortality rate was 10.9%. The distribution of hospital volume by quartiles was as follows; 1st quartile, Q1 (2 or less hospitalizations of TTP per year), 2nd quartile, Q2 (3-5/year), 3rd quartile, Q3, (6-11/year), 4th quartile, Q4 (12 and above). The mean length of stay was 14.4 ± 11.5 days and the mean cost of hospitalization was $ 177546 ± 7736. Overall there was decreasing trend in inpatient mortality with increasing hospital volumes (14.4% vs 12.8% vs 9.8% vs 6.5% from Q1-Q4 respectively; p trend 0.002). This effect was also retained in multivariate analysis adjusting for potential confounders (aOR 0.50; 95% CI 0.26-0.98; p 0.04) (Table 1). Also there was a decreasing trend in the time to plasmapheresis with increasing hospital volume (3.02 vs 2.48 vs 2.27 vs 2.09 from Q1-Q4 respectively, ANOVA p value 0.04) with post hoc analysis significant difference between 4th versus 1st quartile (Tukey p value 0.04). Conclusion: In this retrospective cohort study using a large US inpatient database, we identified a significant association between hospital volume and inpatient mortality. Furthermore, plasmapheresis was initiated earlier in the hospital course at higher volume hospitals and provides a potential mechanism for the survival improvement. Disclosures Podoltsev: Ariad: Consultancy; Incyte: Consultancy; Alexion: Consultancy; CTI biopharma/Baxalta: Consultancy. Huntington: Janssen: Consultancy; Pharmacyclics: Honoraria; Celgene: Consultancy, Other: Travel. Zeidan: AbbVie, Otsuka, Pfizer, Gilead, Celgene, Ariad, Incyte: Consultancy, Honoraria; Takeda: Speakers Bureau; Otsuka: Consultancy.

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Thrombotic Thrombocytopenic Purpura: A Case Series from a Tertiary Care Centre in Northern India

Blood ◽

10.1182/blood-2018-99-110773 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5006-5006

Author(s):

Sanjeev Kumar Sharma ◽

Dharma Choudhary ◽

Meet P. Kumar ◽

Rasika Setia ◽

Vipin Khandelwal ◽

...

Keyword(s):

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Hemolytic Anemia ◽

Case Series ◽

High Index ◽

Medical Emergency ◽

Microangiopathic Hemolytic Anemia ◽

Thrombocytopenic Purpura ◽

Post Transplant ◽

High Index Of Suspicion

Abstract Abstract: Thrombotic thrombocytopenic purpura is a medical emergency with varied clinical manifestations. High index of suspicion with careful evaluation of thrombocytopenia and hemolytic anemia is of paramount importance. Laboratory parameters of microangiopathic hemolytic anemia i.e. schitocytosis and increased LDH and indirect hyperbilirubinemia support the diagnosis. Plasma exchange is the treatment of choice. Post stem cell transplant TTP carries a poorer prognosis. Introduction: Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia associated with fever, renal dysfunction and neurological manifestations. Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange mortality decreases to about less than 10% (1). Recent reports indicate that rituximab can induce remission in the majority of patients with classic TTP (2). We report here 13 cases of TTP who were treated at our hospital in last 4 years. Six of these patients developed features of TTP post allogenic stem cell transplantation. Materials and Methods: The study included retrospective analysis of patients who presented with the features of TTP. Patients with characteristic features of TTP included two or more features among the pentad commonly considered diagnostic of TTP. Evidence of microangiopathic hemolytic anemia and thrombocytopenia were the minimal requirement for the diagnosis with or without fever, renal dysfunction and neurological manifestations. Coagulation profile included prothrombin time and APTT. Liver and kidney function analysis was done in all patients. Response was assessed by clinical and laboratory parameters with monitoring platelet counts, LDH, and schistocytes in the peripheral blood film. Patients with LDH in normal range and platelet counts more than 100,000/µl were considered to have achieved remission. Results: Patients with classic TTP recovered with plasma exchange and/or rituximab. Post-transplant TTP patients had a poorer prognosis as five out of six post-transplant TTP patients died. Discussion: TTP can have a varied clinical presentation and can be associated with many other diseases. Our case series highlight the varied manifestations and associations of TTP and their management and outcome. TTP is a medical emergency and needs high index of suspicion for the diagnosis. In our series, TTP was diagnosed by the findings of thrombocytopenia and hemolytic anemia evidenced by presence of schistocytes in the peripheral blood film and increased LDH, in the absence of coagulopathy. TTP should be suspected in the presence of microangiopathic hemolytic anemia and thrombocytopenia (1,3), and treatment should be started immediately, as delay in treatment can increase the mortality (1). Plasma exchange has changed the prognosis of this highly fatal disease to a highly curable disease. Rituximab has further improved the management of TTP (2). Patients with classic TTP were treated with plasma exchange but 3 patients also required rituximab. All patients with classic TTP are in remission. Transplant-associated microangiopathy (TAM) is a MAHA and thrombocytopenia that occurs after bone marrow transplantation. Patients with post-transplant TTP were diagnosed based on thrombocytopenia and features of microangiopathic hemolytic anemia with schistocytosis and raised LDH, in the absence of coagulopathy. They were treated with FFP and steroids, as plasma exchange is not beneficial for post-transplant TTP (1). Repeated plasma exchange with increased frequency and/or rituximab therapy are the agents of choice in relapsing disease (3). Rituximab is a safe and effective treatment for newly diagnosed TTP, and has been shown to decrease the number of plasma exchange required to achieve remission. We used rituximab in 3 patients and all improved. Post transplant MAHA carried poor prognosis. Conclusion: Diagnosis of TTP requires a high index of suspicion and prompt treatment with plasma exchange, which results in a high cure rate. Rituximab is useful in patients relapsing or showing partial recovery. Plasma exchange has not been reported to be effective in post-transplant TTP. Acknowledgment: We are thankful to Ms Bharti Sharma for compiling the data. Disclosures No relevant conflicts of interest to declare.

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